Sensing the brain’s chemical signals

Nako Nakatsuka earned a place on this year’s MIT Technology Review’s Innovators Under 35 list for her invention of a precise chemical biosensor that empowers researchers to better understand brain processes and diseases such as Alzheimer’s, Major Depression, and Parkinson’s.
Nako Nakatsuka, Senior Scientist in ETH Zurich’s Biosensors and Bioelectronics Lab. (Image: Marianne Lucien / ETH Zurich)

More than 100 billion neurons in the human brain talk to each other non-stop using both electrical and chemical pathways. While researchers have typically focused on the electrical aspects of this communication, ETH Zurich Senior Scientist, Nako Nakatsuka has ventured into the comparably uncharted territory of chemical signaling. Precise chemical sensing is an essential, yet missing piece of the puzzle when it comes to understanding how the brain functions. “There is so much we don’t yet understand about ourselves, like why we might wake up feeling sad today for no apparent reason,” Nakatsuka says. “All of it is driven by our brain chemistry, which we know so little about.”

Biotechnology innovator

On June 30th this year, Nako Nakatsuka was named to the MIT Technology Review’s Innovators Under 35 list for inventing a chemical biosensor that helps neuroscientists better understand how brain cells communicate on a molecular level. To advance the understanding of how psychiatric and neurodegenerative diseases develop, “It is critical to take a step back and question how healthy brain cells, or neurons, communicate,” she says. The advancement of research in neurochemical sensing has been hindered by the challenges of trying to differentiate similarly structured neurochemicals in the sea of interfering molecules in a complex brain environment.

Recognition as a technology innovator, expanded Nakatsuka’s network and prompted not only a multi-disciplinary dialogue, but also new perspectives on the ethical and societal impact of new technologies. Industry too was abuzz with the exciting commercial potential of being able to monitor neurochemical levels.

“Nako’s ideas have the potential to revolutionize biomedicine,” says Professor Janos Vörös, a Principal Investigator in ETH Zurich’s Biosensors and Bioelectronics Lab. “With her limitless enthusiasm, I am convinced that she will be able to make novel nanomaterial-based sensing platforms useful for neuroscience and other scientific areas such as infectious diseases, cancer, and diagnostics for nearly anything we wish to detect.”

Nakatsuka cautions, “We are still in the early, experimental stages of this research, so don’t expect to be able to monitor your brain activity on your Apple watch anytime soon.”

Breakthrough tool for understanding the brain

Working at the intersection of chemistry, engineering, and neuroscience enabled Nako Nakatsuka to develop a chemical biosensor that represents a significant breakthrough potential for advancing analytical science across disciplines. She now deploys her sensors to labs around the world where researchers are monitoring neurotransmitters in complex living biological samples at concentrations that were previously impossible to measure at nanoscale resolutions.

The tool itself is glass pipette with a 10-nanometer tip, so small that it is invisible to the naked eye. By combining DNA sequences and two electrodes, the chemical sensor allows researchers to detect and to measure neurochemicals as they travel through the nanoscale opening of the glass pipette. Nakatsuka aims to further develop her biosensing technology laying the groundwork for future applications in preventative medicine, as well as treatment strategies for brain diseases.

Ikigai - finding passion and purpose

“My life has been a series of lucky coincidences,” she says, but when Nako Nakatsuka recounts her life it is clearly more about passion than coincidence. Often combining her passions for art, sports, and science with purpose, she illustrated the children’s book, “A is for Atom, ABCs for Aspiring Chemists.” Her passion spans generations from starring in “Kids Teach Science Experiments to a Real Scientist” episodes to inspiring her now super fit 89-year-old grandmother to take up a gym membership. From her perspective, “The sky is the limit when you help someone believe that they can do something.”

For Nako Nakatsuka finding her sense of purpose in life or “ikigai” was a matter of perseverance. “Things are always going to be hard at some point, but if I had allowed myself to be consumed by those thoughts, I wouldn’t have been able to move forward…it is sheer grit that gets us through the tough times.” Born in Osaka, Japan and raised in Tokyo, Nakatsuka describes her family life as traditionally Japanese, except for the unconventional decision of her mother to enrol her in the all-girls’, English-speaking, International School of the Sacred Heart. Typically, Japanese children attend a non-denominational, co-educational school system, with a focus on Japanese language, culture, and history. She reflects, “I think being in an international and all-girls’ school was super helpful. I never had to worry about the socio-cultural gender dynamics that exist in co-ed schools. Instead of worrying about self-image, I was able to focus on my studies and athletic goals. I felt accepted for who I was even though I was a bit of a nerd.”

A twist of fate

Nakatsuka found strong female role models throughout her life. At Fordham University in New York City, Professor Ipsita Banerjee challenged her beyond the Bachelor’s degree curriculum with a hands-on research experience working in a bio-nanotechnology lab focused on tissue engineering. There, while still an undergraduate, she earned shared authorship on her first peer reviewed scientific papers. At the University of California, Los Angeles (UCLA) she was mentored by Professor Anne Andrews who trained her to tackle visionary scientific problems while honing her skills in communicating science.

Perhaps it was a twist of fate, however, that led to the impromptu UCLA campus tour that she gave to a visiting professor who described his research at ETH Zurich as one of the best experiences of his scientific career. Nakatsuka confesses that at the time she had never heard of ETH Zurich but was inspired to apply. Janos Vörös invited her to interview and supported her in the highly competitive application for an ETH Zurich Postdoctoral Fellowship. The fellowship made her first two years at ETH Zurich possible. She recounts, “It was during that first visit to ETH Zurich for the interview that I fell in love with the Laboratory of Biosensors and Bioelectronics. I remember feeling that “This is it!”